This application is submitted to NIAID-NIH for consideration for a Physician Scientist Award. The program is designed to i) train the Candidate in fundamental molecular virology and cell biology to enable him to ii) carry out the investigation of HIV-1 infection of bone marrow mononuclear cells (BMMC) and potential mechanisms of HIV-1 associated hematological abnormalities; iii) to gain needed theoretical and practical competence to conduct an independent research career. To acquire fundamental training and expertise in independent experimental design and analysis, a research focus suited to the clinical training and experience of the Candidate and the program of the Sponsor has been selected: HIV infection in BMMC and its impact on AIDS pathogenesis. This application describes a five-year program of two phases; the Candidate's progress in this program will be formally evaluated at scheduled intervals. Phase I of this program has three parts: i) intensive training in research techniques; ii) preliminary studies in HIV infection in BMMC; iii) instruction in fundamental subjects related to program theme. Research training will take place by apprenticeship and participation in ongoing programs in the Sponsor's laboratory including molecular genetics and recombinant DNA technology, cell and virological culture, detection of HIV-1 and its expressional state in specific cell types, and reconstruction and perturbation of bone marrow microenvironment. As experimental competence is gained, the Candidate will begin the specific research program of Phase II. Its goals are to: i) analyze the frequency of HIV-1 infection, its expression, and its target cell types in BMMC of HIV-1 infected persons; ii) analyze the mechanism of HIV-1 entry and expression in BMMC infected in culture; iii) establish and perturb culture systems differentiation of specific progenitor cells; and iv) evaluate anti- retroviral drugs and recombinant anti-sense viral RNA for modulation of HIV-1 infection in BMMC.